α-Difluoromethylornithine Alters Calcium Signaling in Platelet-derived Growth Factor-stimulated A172 Brain Tumor Cells in Culture

α-Difluoromethylornithine Alters Calcium Signaling in Platelet-derived Growth Factor-stimulated A172 Brain Tumor Cells in Culture
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α-二氟甲基鸟氨酸改变培养中血小板衍生生长因子刺激的 A172 脑肿瘤细胞中的钙信号传导

DOI:
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发表时间:
1992
期刊:
影响因子:
--
通讯作者:
L. Marton
L. Marton
中科院分区:
--
文献类型:
--
作者:
B. Feuerstein;J. Szöllősi;H. Basu;L. Marton

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α -二氟甲基鸟氨酸(DFMO)是多胺生物合成酶鸟氨酸脱羧酶的不可逆抑制剂,可抑制脑肿瘤细胞系的生长,目前正在进行脑肿瘤治疗的临床试验。血小板源性生长因子(PDGF)被认为调节正常和肿瘤性星形胶质细胞的前体细胞的生长和发育;钙信号被认为在PDGF信号的转导中起作用。应用激光荧光图像分析仪、流式细胞仪和荧光分光光度法研究了DFMO对PDGF诱导的A172人胶质母细胞瘤细胞钙信号的影响。用5 mm DFMO治疗4天显著缩短了PDGF诱导的钙信号。腐胺和亚精胺处理后4 h,多胺含量增加,但腐胺处理后10 h以上,24 h内,多胺含量增加,但多胺含量增加。DFMO对细胞内钙释放或质膜钙通道开放和关闭的时间没有显著影响。这些发现支持了钙信号可能是多胺代谢抑制剂的靶点的观点。
α -Difluoromethylornithine (DFMO), an irreversible inhibitor of the polyamine biosynthetic enzyme ornithine decarboxylase, inhibits the growth of brain tumor cell lines and is undergoing clinical trials as a treatment for brain tumors. Platelet-derived growth factor (PDGF) is thought to regulate the growth and development of precursors of both normal and neoplastic astrocytic cells; calcium signaling is thought to play a role in the transduction of PDGF signals. Using laser fluorescence image cytometry, flow cytometry, and spectrofluorometry, we studied the effect of DFMO on the calcium signals induced by PDGF in A172 human glioblastoma cells. Four days of treatment with 5 mm DFMO substantially shortened PDGF-induced calcium signals. The effect was reversed more than 10 h but less than 24 h after putrescine treatment, even though polyamines were repleted 4 h after putrescine and spermidine were added. DFMO did not substantially affect intracellular calcium release or the timing of the opening and closing of plasma membrane calcium channels. These findings support the notion that calcium signaling may be a target for inhibitors of polyamine metabolism.
源自人类恶性神经胶质瘤细胞系 U-251MG 的生长因子。
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DOI: --
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